Table12_Integrative epigenome profiling of 47XXY provides insights into whole genomic DNA hypermethylation and active chromatin accessibility.XLS

Klinefelter syndrome (KS, 47XXY) is a disorder characterized by sex chromosomal aneuploidy, which may lead to changes in epigenetic regulations of gene expression. To define epigenetic architectures in 47XXY, we annotated DNA methylation in euploid males (46XY) and females (46XX), and 47XXY individuals using whole genome bisulfite sequencing (WGBS) and integrated chromatin accessbilty, and detected abnormal hypermethylation in 47XXY. Furthermore, we detected altered chromatin accessibility in 47XXY, in particular in chromosome X, using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) in cultured amniotic cells. Our results construct the whole genome-wide DNA methylation map in 47XXY, and provide new insights into the early epigenomic dysregulation resulting from an extra chromosome X in 47XXY.

克莱费尔特综合征（Klinefelter syndrome, KS, 47XXY）是一类以性染色体非整倍体为特征的疾病，可引发基因表达的表观遗传调控异常。为明确47XXY核型个体的表观遗传组架构，我们采用全基因组亚硫酸氢盐测序（whole genome bisulfite sequencing, WGBS），对整倍体男性（46XY）、女性（46XX）及47XXY个体的DNA甲基化水平进行注释，并整合染色质可及性数据；同时在培养羊膜细胞中借助转座酶可及性染色质测序（Assay for Transposase-Accessible Chromatin sequencing, ATAC-seq）开展分析，检测到47XXY核型个体存在异常高甲基化现象，且其染色质可及性发生改变，尤以X染色体区域最为显著。本研究构建了47XXY核型个体的全基因组DNA甲基化图谱，为解析额外X染色体导致的47XXY早期表观基因组失调提供了新的研究视角。